The objective of the proposed research is to determine: 1) the ontogenesis of normal cellular electrophysiologic properties of perinatal hearts; 2) the effects of autonomic agonists and antagonists on transmembrane action potentials and automaticity of perinatal hearts. Standard microelectrode techniques will be used to study the ventricular specialized conducting system, right atrial preparations containing the sinus node, and working myocardium. The effects of adrenergic and cholinergic agonists and antagonists on cardiac electrophysiology will be determined using isolated, superfused cardiac tissues obtained from fetuses of early, middle, and late gestation. Finally, we will perform a chemical sympathectomy of pregnant and neonatal dogs using 6-hydroxydopamine to determine the effects of partial and complete inhibition of sympathetic nervous system development on the ontogenesis of cardiac cellular electrophysiologic characteristics. Results of studies performed to date indicate that there is a strong correlation of cellular electrophysiologic properties and automaticity with advancing fetal development. The information obtained from the proposed research project will be of value to our understanding of the normal development of cellular electrophysiologic properties and also to our understanding of disturbances in cardiac rate and rhythm which may arise as a result of maternal administration of pharmacological agents which affect cardiac function in the fetus.